World Health Organization Guidelines for Containment of Poliovirus Following Type-Specific Polio Eradication — Worldwide, 2015

Morbidity and Mortality Weekly Report

Nicoletta Previsani, PhD1; Rudolph H. Tangermann, MD1; Graham Tallis1; Hamid S. Jafari, MD1

In 1988, the World Health Assembly of the World Health Background Organization (WHO) resolved to eradicate polio worldwide. The Endgame Plan (3) set the goal of eradicating WPV and Among the three wild poliovirus (WPV) types (type 1, type 2, VDPV. Achieving this goal requires 1) detection of circulating and type 3), WPV type 2 (WPV2) has been eliminated in polioviruses and interruption of transmission; 2) sequential the wild since 1999, and WPV type 3 (WPV3) has not been cessation of the use of type-specific OPV to eliminate the risks reported since 2012. In 2015, only Afghanistan and Pakistan for vaccine-associated paralytic poliomyelitis, chronic VDPV have reported WPV transmission (1). On May 25, 2015, all infections of immunodeficient persons, and outbreaks of WHO Member States endorsed World Health Assembly reso- circulating VDPV (cVDPV) (6,7); and 3) implementation of lution 68.3 on full implementation of the Polio Eradication and measures for the safe handling and containment of polioviruses Endgame Strategic Plan 2013–2018 (2,3) (the Endgame Plan), to minimize the risks for facility-associated reintroduction and with it, the third Global Action Plan to minimize poliovirus of virus into polio-free communities. The first step toward facility-associated risk (4) (GAPIII). All WHO Member States OPV cessation will be the global, synchronized withdrawal have committed to implementing appropriate containment of of OPV2, which has caused approximately 90% of cVDPV WPV2 in essential laboratory and vaccine production facili- cases since WPV2 was last reported in 1999. OPV2 withdrawal ties* by the end of 2015 and of type 2 oral poliovirus vaccine will be accomplished by replacing trivalent OPV (tOPV) with (OPV2) within 3 months of global withdrawal of OPV2, bivalent OPV (bOPV, protecting against types 1 and 3 in all which is planned for April 2016 (5). This report summarizes countries using OPV for routine immunization, preceded critical steps for essential laboratory and vaccine production by the introduction of a minimum of 1 dose of inactivated facilities that intend to retain materials confirmed to contain poliovirus vaccine (IPV), which protects against all three or potentially containing type-specific WPV, vaccine-derived virus types (5). Approval to confirm the global switch from poliovirus (VDPV), or OPV/Sabin viruses, and steps for nones- tOPV to bOPV, anticipated in April 2016, will follow review sential facilities† that process specimens that contain or might in October 2015 of whether a number of readiness criteria contain polioviruses. National authorities will need to certify are met, including progress toward completion of the initial that the essential facilities they host meet the containment phase of poliovirus containment activities and establishment of requirements described in GAPIII. After certification of WPV readiness for appropriate handling of residual type 2 materials, eradication, the use of all OPV will cease; final containment as described below. of all polioviruses after polio eradication and OPV cessation will minimize the risk for reintroduction of poliovirus into a Methods polio-free world. The Endgame Plan includes phased withdrawal of OPV strains. GAPIII was aligned to the Endgame Plan and comprises * A facility designated by the ministry of health or other designated national three phases (Figure): Phase I, Preparation for containment body or authority as serving critical national or international functions that of poliovirus type 2, lasting until global readiness criteria for involve handling and storage of needed poliovirus infectious materials or potentially infectious materials under conditions set out in GAPIII. the switch are met (current target is end of 2015); Phase II, † Any facility that is likely to investigate new WPV2, type 2 attenuated vaccine- Poliovirus type 2 containment, lasting until all WHO regions derived poliovirus (aVDPV2), type 2 circulating vaccine-derived poliovirus certify WPV elimination; and Phase III, Final poliovirus con- (cVDPV2), or inactivated type 2 vaccine-derived poliovirus (VDPV2) isolates, or new fecal or respiratory samples originating from recent OPV-using countries, tainment. National authorities in all countries are currently and adopts and implements 1) safe and secure working practices based on a tasked with completing Phase I and preparing for Phase II risk assessment and the implementation of appropriate biorisk management systems as described in GAPIII, 2) a nonretention policy for WPV2 materials (Table 1). as of the beginning of Phase IIa of the poliovirus type 2 containment period, The controls described in GAPIII reflect containment best and 3) a nonretention policy for OPV2/Sabin2 materials as of the beginning practices, and are largely derived from the European Committee of Phase IIb of the poliovirus type 2 containment period. for Standardization Workshop Agreement 15793 (2011) — Laboratory Biorisk Management (8), with input from leaders in the field of poliovirus transmission and biorisk management.

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FIGURE. Schematic diagram of the phased poliovirus containment, by type of facility — worldwide

Phase I: Phase II: Phase III: Preparation for containment Poliovirus type 2 containment period Final poliovirus containment of poliovirus type 2 OPV2 withdrawal

Certi cation of WPV Global eradication by all six readiness WHO regions criteria bOPV met cessation

Inventory, Essential destruction, facilities IIIa: Final containment of all WPV preparation for Ctmt IIa: WPV2 containment holding WPV certi ca- containment tion

Essential Destruction, facilities holding IIIb: Final containment of all preparation for IIb: OPV2/Sabin2 poliovirus containment OPV/Sabin only containment Containment OPV/Sabin polioviruses (no WPV) certi cation

Destruction, Nonessential safe handling, Safe handling of new samples potentially containing poliovirus material in nonessential laboratories Adopt facilities no storage safe measures

No containment Adoption of safe-handling measures Containment of WPV2, OPV2/Sabin2; nal containment of all OPV/Sabin polioviruses Final containment of all WPV

Abbreviations: WPV = wild poliovirus; OPV = oral poliovirus vaccine.

Rationale production and storage of monovalent OPV stockpiles of each Reintroduction of WPV from a poliovirus facility after type- type, vaccine quality assurance, diagnostic reagent production, specific eradication risks the potentially disastrous consequence and crucial research. Each essential poliovirus facility should of reestablishing WPV transmission. When OPV use stops, manage biorisk appropriately to minimize the risk for virus many countries will maintain high population coverage with reintroduction into the community, with effective national IPV, other countries will have suboptimal IPV coverage, and certification and WHO verification programs to assure com- still others might discontinue use of IPV and all national pliance with GAPIII. The risk for a poliovirus reintroduction polio immunization activities. Reintroduction of an OPV/ can further be minimized by ensuring that essential facilities Sabin strain from a facility creates risks for unrecognized virus are located in areas with high levels of population immunity transmission, reversion to cVDPV, and reestablishment of and acute flaccid paralysis and environmental surveillance, poliovirus transmission. supplemented by efficient public health and response capac- Most countries will have no need to retain polioviruses ity (Table 2). Minimizing the number of essential facilities following WPV eradication and cessation of OPV use. worldwide will further reduce the magnitude of risk, facili- Facility-associated risks in these countries can be eliminated tate national and international oversight, and strengthen the by a thorough nationwide search for, and destruction of, all likelihood that global containment standards can be met and infectious and potentially infectious materials, including WPV, successfully maintained. VDPV, and OPV/Sabin viruses. Some countries will host a limited number of essential laboratory and vaccine production Policy and Implementation facilities that serve critical program and research functions, Phase I: Preparation for containment of all type 2 polio- including production of IPV and Sabin-IPV (IPV produced viruses. Phase I is currently in progress. Phase I for WPV2 using attenuated strains from the Sabin oral vaccine as seed), will continue until the conditions of global readiness for

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TABLE 1. Phased implementation of poliovirus containment activities in the third Global Action Plan (GAPIII)* to minimize poliovirus facility- associated risk, worldwide Prerequisites Begins Target for completion Key activities Phase I: Preparation for containment of PV type 2 None Ongoing For WPV2: global readiness for OPV2 • Governments, institutions, and laboratory and withdrawal (target for global vaccine production facilities informed about the readiness review is October 2015) upcoming need for type-specific poliovirus For OPV2/Sabin2: 3 months after the containment withdrawal of tOPV • Inventory and survey of laboratory facilities and vaccine production facilities handling or storing infectious or potentially infectious poliovirus materials Essential facilities†: • National certification of WPV2-holding laboratories and IPV production facilities Nonessential facilities§: • Destruction of unneeded PV material • Transfer of needed PV type 2 material to essential laboratory facilities • If specimen investigations continue, adoption of nonretention policy for new WPV2 isolates, to be implemented in Phase IIa Phase IIa: WPV2 containment Elimination of circulating As soon as the criteria for global After all six WHO Regions have Essential facilities†: WPV2 readiness for OPV2 withdrawal are certified WPV eradication • Handle and store WPV2 materials in “Containment Elimination of persistent met (target is January 2016) of WPV2” conditions outlined in GAPIII cVDPV2 Nonessential facilities§: • Destroy remaining unneeded OPV2 material • Transfer needed OPV2 material to certified essential laboratory facilities Nonessential facilities that continue specimen investigations¶: • Implement nonretention policy • Destroy unneeded recently isolated PV material • Transfer needed recently isolated PV material to certified essential facilities Phase IIb: OPV/Sabin PV type 2 (OPV2/Sabin2) containment Licensed, available bOPV Within 3 months of global tOPV to Within 3 months of global bOPV Essential facilities†: (types 1 and 3) bOPV switch (target for global cessation (planned 1 year after • Handle and store OPV materials in “Containment of Global IPV introduction switch is April 2016) global certification of WPV OPV2/Sabin2 polioviruses” conditions outlined in Global tOPV-bOPV switch eradication) GAPIII Phase IIIa: Final containment of all WPV after polio eradication 3 years pass without As soon as all six WHO Regions Long-term eradication (beyond Essential facilities†: isolation of WPV certify WPV eradication global bOPV cessation) • Handle and store all WPV materials in “Final containment of all WPV” conditions, as outlined in GAPIII Phase IIIb: Final biocontainment of all OPV/Sabin PV after bOPV cessation Global bOPV cessation Within 3 months of global bOPV Long-term eradication (beyond Essential facilities†: cessation (planned 1 year after global global bOPV cessation) • Handle and store OPV materials in “Final certification of WPV eradication) containment of all OPV/Sabin polioviruses” conditions, as outlined in GAPIII Abbreviations: bOPV = bivalent oral polio vaccine (types 1 and 3); cVDPV2 = type 2 circulating vaccine-derived poliovirus; GAPIII = third Global Action Plan to minimize poliovirus facility-associated risk; IPV = inactivated poliovirus vaccine; OPV = oral poliovirus vaccine; OPV2 = type 2 OPV; PV = poliovirus; tOPV = trivalent OPV (types 1, 2 and 3); WHO = World Health Organization; WPV = wild poliovirus; WPV2 = type 2 WPV. * Available at http://www.polioeradication.org/Portals/0/Document/Resources/PostEradication/GAPIII_2014.pdf. † A facility designated by the ministry of health or other designated national body or authority as serving critical national or international functions that involve handling and storage of needed poliovirus infectious materials or potentially infectious materials under conditions set out in GAPIII. § Any facility that is likely to investigate new WPV2, aVDPV2, cVDPV2 or iVDPV2 isolates, or new fecal or respiratory samples originating from recent OPV-using countries, and adopts and implements a) safe and secure working practices based on a risk assessment and the implementation of appropriate biorisk management systems as described in GAPIII, b) a nonretention policy for WPV2 materials as of the beginning of Phase IIa of the poliovirus type 2 containment period, and c) a nonretention policy for OPV2/Sabin2 materials as of the beginning of Phase IIb of the poliovirus type 2 containment period. ¶ All nonessential laboratories investigating new WPV2; aVDPV2, cVDPV2, or iVDPV2 isolates, or new fecal and respiratory samples originating from recent OPV-using countries.

OPV2 withdrawal have been met (Table 1), which include Phase I for OPV2/Sabin2 will continue until 3 months after elimination of persistent cVDPV2 and certification of WPV2 the switch from tOPV to bOPV. Surveyed national laboratories eradication, currently planned for review in October 2015. should include 1) all public or private facilities working with

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TABLE 2. Containment safeguards to minimize poliovirus facility-associated risks after type-specific eradication of wild polioviruses and sequential cessation of oral polio vaccine use, worldwide Poliovirus type 2 biocontainment Final poliovirus biocontainment (phases IIa and IIb) (phases IIIa and IIIb) Safeguards All type 2 polioviruses All OPV/Sabin polioviruses All wild polioviruses Primary safeguards: prevention of infection with and release of contaminated materials Operator protection* Yes Yes Yes Decontamination of materials/equipment Yes Yes Yes Dedicated effluent treatment plant No† No† Yes§ Air/exhaust treatment No No Yes¶ Secondary safeguards: population immunity in country hosting facility Number of IPV doses ≥1 ≥1 ≥3 IPV coverage = DTP3 coverage** = DTP3 coverage** >90% Tertiary safeguards: environment and location Situating facilities in areas with low transmission No No Yes potential for wild polioviruses * Because the operator is considered to be one of the sources of release of poliovirus from the facility, specific measures of protection are required, including use of personal protective equipment, use of primary containment devices, and vaccination. † Untreated release into a closed sewage system with secondary effluent treatment in facility location (Note: all waste from facilities, potentially containing live poliovirus, should be inactivated before release through adequate and validated inactivation procedures. For facilities without a dedicated effluent treatment plant, this would normally be done through the application of heat or chemicals as part of a validated treatment process. Under no circumstances should raw poliovirus containing effluents be discharged to drains, unless the effluent treatment plant has been designed and validated to handle such effluents, effectively acting as part of the primary containment system). § Facility effluent treatment before release into closed sewage system with secondary or greater effluent treatment in facility location. ¶ HEPA (high efficiency particulate arresting) filtration on exhaust air. ** Diphtheria-tetanus-pertussis (DTP3) vaccine third dose coverage; available at http://www.who.int/gho/immunization/dtp3/en/.

WPV2/VDPV2 and all facilities working with OPV2/Sabin2 after all six WHO regions have certified WPV eradication. or with fecal or respiratory materials that could contain WPV2, Phase IIb begins within 3 months of withdrawal of tOPV and VDPV2, or OPV2/Sabin2 (collected at a time and place when the switch to bOPV, and ends within 3 months after global OPV was in use), and 2) all public or private facilities that bOPV cessation. Essential poliovirus facilities handling and might have collections of infectious or potentially infectious storing WPV2 or OPV2/Sabin2 materials in Phase II must WPV2, VDPV2 or OPV2/Sabin2 materials of any origin that be certified to implement containment procedures, and be are maintained for any reason. regularly reassessed against WPV2 containment provisions Facilities that retain specimens that might contain WPV2/ described in GAPIII, including primary and secondary safe- VDPV2 viruses must destroy or contain such materials before guards (Table 2). Once Phase II begins, facilities that have not Phase IIa can begin. Facilities that wish to retain specimens that received national certification for WPV2 containment will might contain OPV2/Sabin2 viruses (i.e., fecal or respiratory no longer be permitted to handle and store WPV2 materials. samples collected in places when OPV was in use) must destroy Countries or concerned facilities may apply to WHO through or contain such materials before commencement of Phase IIb. their national authorities for verification of containment in Laboratories wishing to retain historic collections of clinical essential poliovirus facilities, certified by the ministries of materials potentially containing polioviruses, but that are not health or other designated national authority, and declared to planning to implement the poliovirus containment measures meet all biorisk management criteria consistent with GAPIII. described in GAPIII, must explore transfer options with des- Phase III: Final poliovirus containment. Phase III also has ignated certified essential poliovirus facilities for handling and two parts (Phases IIIa and IIIb). Phase IIIa (final containment storage arrangements. of all WPV after polio eradication) begins when all six WHO Phase II: Poliovirus type 2 containment period. Phase II regions have completed the certification of WPV eradication, at begins as soon as the criteria for global readiness for OPV2 least 3 years after the last isolation of WPV (Table 1). Certified withdrawal are met (5) and is currently planned for January essential laboratories and IPV production facilities handling 2016 (Table 1). This phase comprises two parts: the first and storing any WPV or VDPV materials must implement (Phase IIa) addresses the containment of WPV2, and the sec- final containment of all WPV provisions, including primary, ond (Phase IIb) the containment of OPV2/Sabin2 polioviruses secondary, and tertiary safeguards (Table 2). Once Phase III in certified essential facilities. Phase IIa begins after elimination begins, facilities that have not received national certification of persistent cVDPV2 and certification of WPV2 eradication, for final containment of all WPV will no longer be permitted at the time of global readiness for OPV2 withdrawal, and ends to handle and store any WPV materials. At the time of global

916 MMWR / August 28, 2015 / Vol. 64 / No. 33 Morbidity and Mortality Weekly Report bOPV cessation (currently planned for 1 year after the global meeting the requirements for full containment certificates are declaration of WPV eradication), all countries must recall and addressed within pressing timelines. The proposed mechanisms destroy bOPV stocks. WHO will provide specific implementa- will provide some degree of flexibility as facilities make the tion guidelines for collection and destruction of bOPV from required changes, and national authorities and other governing designated collection points, health facilities, or private prac- bodies develop the required capacity to implement certifica- titioners, and national and subnational storage facilities (9). tion requirements. Phase IIIb (final containment of all OPV poliovirus after The final containment of all WPV/VDPVs, including bOPV cessation) will begin 3 months after global bOPV cessa- types 1 and 3, is approaching. After WPV transmission has tion (Figure) (Table 1). Certified essential poliovirus laborato- been stopped, final containment of all polioviruses will mini- ries and Sabin-IPV vaccine production facilities handling and mize the risk for poliovirus reintroduction into a polio-free storing OPV/Sabin materials (but no WPV) must implement world once all OPV use is phased out. As is the case with final provisions for containment of all OPV/Sabin polioviruses, variola virus, containment requirements will have to be regu- including primary and secondary safeguards (Table 2). Once larly assessed and maintained, until a global decision is made Phase IIIb begins, facilities that have not received national cer- to destroy all remaining poliovirus materials and prohibit any tification for final containment of all OPV/Sabin polioviruses de novo synthesis. will no longer be permitted to handle and store OPV/Sabin 1Polio Eradication Department, World Health Organization. materials. Within 6 months of bOPV cessation, all countries Corresponding author: Nicoletta Previsani, PhD, [email protected], must submit documentation that requirements for final con- 41-22-791-2866. tainment of all OPV/Sabin polioviruses have been met. References Discussion 1. Hagan JE, Wassilak SGF, Craig AS, et al. Progress toward polio An estimated 500 facilities worldwide are currently holding eradication—worldwide, 2014–2015. MMWR Morb Mortal Wkly Rep 2015;64:527–31. type 2 polioviruses. One of the goals of poliovirus containment 2. World Health Organization. Poliomyelitis. Geneva, Switzerland: Sixty- is to reduce this number substantially (10), dissuading candi- eighth World Health Assembly Resolution WHA68.3, May 26, 2015. date facilities not meeting the GAPIII containment criteria for Available at http://apps.who.int/gb/ebwha/pdf_files/WHA68/A68_ R3-en.pdf. essential facilities from holding any polioviruses. 3. Global Polio Eradication Initiative. Polio Eradication and Endgame It is important to note that poliovirus diagnostic laboratories Strategic Plan 2013–2018. Geneva, Switzerland: Global Polio Eradication will continue to be critical for surveillance and will remain so Initiative; 2013. Available at http://www.polioeradication.org/portals/0/ for years to come. Poliovirus diagnostic laboratories are not document/resources/strategywork/endgamestratplan_20130414_eng.pdf. 4. World Health Organization. GAPIII: WHO global action plan to required to become certified essential poliovirus facilities to minimize poliovirus facility-associated risk. Geneva, Switzerland: World continue to perform their jobs, as long as they do not retain Health Organization; 2014. Available at http://www.polioeradication. live polioviruses. However, laboratories that perform reference org/Portals/0/Document/Resources/PostEradication/GAPIII_2014.pdf. 5. Immunization Systems Management Group of the Global Polio (and diagnostic) functions need to retain live polioviruses and Eradication Initiative. Introduction of inactivated poliovirus vaccine and thus be certified to meet the criteria for essential poliovirus switch from trivalent to bivalent oral poliovirus vaccine—worldwide, facilities. Only designated essential poliovirus facilities that 2013–2016. MMWR Morb Mortal Wkly Rep 2015;64:699–702. 6. Platt LR, Estívariz CF, Sutter RW. Vaccine-associated paralytic are certified to meet GAPIII containment requirements will poliomyelitis: a review of the epidemiology and estimation of the global handle and store polioviruses. burden. J Infect Dis 2014;210(Suppl 1):S380–9. The timeline presented in GAPIII for the type-specific con- 7. Diop OM, Burns CC, Sutter RW, Wassilak SG, Kew OM. Update on tainment of polioviruses is short, both for candidate essential vaccine-derived polioviruses—worldwide, January 2014–March 2015. MMWR Morb Mortal Wkly Rep 2015;64:640–6. poliovirus facilities to be assessed and certified to meet GAPIII 8. European Committee for Standardization. Laboratory biorisk requirements, and for national authorities responsible for management. CEN Workshop Agreement 15793:2011, September containment to deliver containment certificates. However, 2011. Available at http://www.uab.cat/doc/CWA15793_2011. 9. World Health Organization. The switch from tOPV to bOPV continuation of polio vaccine production, surveillance, and Implementation guidelines. Geneva, Switzerland: World Health research is critical and must continue. To help manage the Organization; 2014. Available at http://www.who.int/immunization/ practical challenges associated with implementation of contain- diseases/poliomyelitis/endgame_objective2/oral_polio_vaccine/switch_ guidelines-april2015.pdf?ua=1. ment for essential laboratory and vaccine production facili- 10. Dowdle W, van der Avoort H, de Gourville E, et al. Containment of ties, interim certification of containment has been proposed. polioviruses after eradication and OPV cessation: characterizing risks to Interim certification would allow containment certification improve management. Risk Anal 2006;26:1449–69. to proceed during the endgame phases of eradication in a controlled and structured manner, as issues associated with

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Human Plague — United States, 2015

Natalie Kwit, DVM1,2; Christina Nelson, MD2; Kiersten Kugeler, PhD2; Jeannine Petersen, PhD2; Lydia Plante, MSPH3; Hayley Yaglom, MPH3; Vicki Kramer, PhD4; Benjamin Schwartz, MD5; Jennifer House, DVM6; Leah Colton, PhD6; Amanda Feldpausch, MPH7; Cherie Drenzek, DVM7; Joan Baumbach, MD8; Mark DiMenna, PhD9; Emily Fisher, MD1,10; Emilio Debess, DVM10; Danielle Buttke, DVM11; Matthew Weinburke, MPH11; Christopher Percy, MD12; Martin Schriefer, PhD2; Ken Gage, PhD2; Paul Mead, MD2

On August 25, 2015, this report was posted as an MMWR The mortality rate for untreated plague has ranged from Early Release on the MMWR website (http://www.cdc.gov/mmwr). 66% to 93%; however, in the antibiotic era, mortality has been Since April 1, 2015, a total of 11 cases of human plague reduced to approximately 16% (4). Prompt treatment with have been reported in residents of six states: Arizona (two), antimicrobials such as aminoglycosides, fluoroquinolones, or California (one), Colorado (four), Georgia (one), New doxycycline greatly improves outcome (4). Mexico (two), and Oregon (one). The two cases in Georgia Health care providers should consider the diagnosis of plague and California residents have been linked to exposures at or in any patient with compatible signs or symptoms, residence near Yosemite National Park in the southern Sierra Nevada or travel in the western United States, and recent proximity to Mountains of California. Nine of the 11 patients were male; rodent habitats or direct contact with rodents or ill domestic median age was 52 years (range = 14–79 years). Three patients animals. Suspicion of plague should prompt 1) collection of aged 16, 52, and 79 years died. blood, bubo aspirate, or sputum samples for Y. pestis diag- Plague is a rare, life-threatening, flea-borne zoonosis caused nostic testing; 2) implementation of isolation and respiratory by the bacterium Yersinia pestis. During 2001–2012, the annual droplet precautions for patients with respiratory involve- number of human plague cases reported in the United States ment; 3) immediate antibiotic treatment (before laboratory ranged from one to 17 (median = three cases) (1). It is unclear confirmation); and 4) notification of public health officials. why the number of cases in 2015 is higher than usual. Plague Y. pestis–specific testing is available at state health laboratories. circulates among wild rodents and their fleas in rural and Recommendations for diagnostic testing and antibiotic treat- semirural areas in the western United States (2). Transmission ment are available at http://www.cdc.gov/plague/healthcare/ to humans occurs through the bite of infected fleas, direct clinicians.html. Misidentification of Y. pestis as Pseudomonas contact with infected body fluids or tissues, or inhalation of luteola and other organisms through the use of automated respiratory droplets from ill persons or animals, including ill bacterial identification systems has been reported (5). domesticated cats and dogs (3). The usual incubation period Persons engaging in outdoor activities in areas where plague between exposure and illness onset is 2–6 days. is endemic should wear long pants when possible and use In humans, plague is characterized by the sudden onset of insect repellent on clothing and skin. Persons also should avoid fever and malaise, which can be accompanied by abdominal direct contact with ill or dead animals and never feed squirrels, pain, nausea, and vomiting. There are three main forms of chipmunks, or other rodents. In addition, pet owners should plague, depending upon the route of infection. Bubonic regularly use flea control products on their pets and consult a plague, resulting from the bite of an infected flea, accounts for veterinarian if their pet is ill. Rodent habitat can be reduced approximately 80%–85% of cases; patients develop a “bubo,” around the home by removing brush, clutter, and potential a painful swelling of one or several lymph nodes that progresses rodent food sources such as garbage or pet food. Additional during the first few days of illness. Septicemic plague, account- information on prevention of plague is available at http://www. ing for approximately 10% of cases, can occur from a flea bite cdc.gov/plague/prevention/index.html. or from direct contact with infectious fluids; infection spreads 1Epidemic Intelligence Service, CDC; 2Division of Vector-Borne Diseases, directly through the bloodstream with no localizing signs. National Center for Emerging and Zoonotic Infectious Diseases, CDC; Primary pneumonic plague, occurring in approximately 3% 3Arizona Department of Health Services; 4California Department of Public Health; 5Los Angeles County Department of Public Health, California; of plague patients, results from aerosol exposure to infective 6Colorado Department of Public Health and Environment; 7Georgia droplets and is characterized by a fulminant primary pneumo- Department of Public Health; 8New Mexico Department of Health; nia. Secondary pneumonic plague can result from the spread 9Albuquerque Environmental Health Department, New Mexico; 10Oregon Health Authority; 11National Park Service; 12Navajo Area Indian Health Service. of Y. pestis to the lungs in patients with untreated bubonic or septicemic infection. Corresponding author: Natalie Kwit, [email protected], 970-266-3587.

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References 4. Kugeler KJ, Staples JE, Hinckley AF, Gage KL, Mead PS. Epidemiology of human plague in the United States, 1900–2012. Emerg Infect Dis 1. Adams DA, Jajosky RA, Ajani U, et al. Summary of notifiable diseases— 2015;21:16–22. United States, 2012. MMWR Morb Mortal Wkly Rep 2014;61:1–121. 5. CDC. Notes from the field: two cases of human plague—Oregon, 2010. 2. CDC. Plague. Atlanta, GA: US Department of Health and Human MMWR Morb Mortal Wkly Rep 2011;60:214. Services, CDC; 2015. Available at http://www.cdc.gov/plague/. 3. Runfola JK, House J, Miller L, et al. Outbreak of human pneumonic plague with dog-to-human and possible human-to-human transmission—Colorado, June–July 2014. MMWR Morb Mortal Wkly Rep 2015;64:429–34.

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